PuSH - Publication Server of Helmholtz Zentrum München

Becker, K.-F. ; Kremmer, E. ; Eulitz, M. ; Schulz, St.* ; Mages, J. ; Handschuh, G.* ; Wheelock, M.J.* ; Cleton-Jansen, A.-M.* ; Höfler, H. ; Becker, I.*

Functional allelic loss detected at the protein level in archival human tumours using allele-specific E-cadherin monoclonal antibodies.

J. Pathol. 197, 567-574 (2002)
Open Access Green as soon as Postprint is submitted to ZB.
Immunohistochemical analysis has been used to show that expression of the homophilic cell-to-cell adhesion molecule, E-cadherin, is frequently altered in human cancers, including gastric and breast carcinoma. Besides genetic down-regulation, structural mutations such as in-frame deletions of exon 8 and exon 9 were frequently found; these may affect the binding of monoclonal antibodies used for immunohistochemical analysis. In this study it was found that antibodies HECD-1 and E9, two monoclonal antibodies often used in E-cadherin immunoanalysis, react with epitopes present at least in part in exon 8 and exon 9, respectively. This study generated and characterized a mutation-specific monoclonal antibody, E-cad delta 8-1, reacting with the mutant protein lacking exon 8 but not with the wild-type molecule. By using E-cad delta 8-1 and HECD-1, it was possible separately to analyse the immunoreactivity of mutant and normal E-cadherin proteins, respectively, in an allele-specific manner in archival material. A similar analysis was performed using E9 and the previously characterized mutation-specific antibody E-cad delta 9-1. Typically, in gastric and breast cancer harbouring E-cadherin splice site gene mutations, the mutant proteins were expressed but the wild-type protein was not detected in malignant tissues. These results indicate that variant-specific monoclonal antibodies can be used to identify differentially expressed E-cadherin proteins. For immunohistochemical analysis of E-cadherin, at least two different monoclonal antibodies should be used to exclude alterations of the epitopes resulting in failure to detect a mutant protein.
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords gene mutation; gastric cancer; breast cancer; immunohistochemistry
ISSN (print) / ISBN 0022-3417
e-ISSN 1096-9896
Journal Journal of Pathology, The
Quellenangaben Volume: 197, Issue: , Pages: 567-574 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
Institute of Molecular Immunology (IMI)